The long-term objectives of this project are to arrive at an understanding of how the nervous system generates behavior and how its neuronal components and circuitry arise during ontogeny. To this end, we have been studying the structure, function and development of the nervous system of leeches for the past ten years. The research plan proposed in the application concerns the development of the nervous system in embryos of the neurologically and embryologically highly favorable leeches Haementeria ghilianii, Helobdella triserialis and Theromyzon rude. Although leeches are phyletically remote from mammals, it can be expected that this project will provide insights of general relevance for understanding developmental mechanisms, including those governing normal and abnormal human development. Our specific aim are: 1) To investigate the developmental mechanism of mutual avoidance of growing axon branches belonging to the same neuron that was found to be operative in the establishment of sensory fields in the embryonic leech skin and to obtain experimental support for the hypothesis that this recognition is based on the detection of coherent electrical activity. 2) To examine the possible guidance role of identified peripheral neuronal cell bodies and of identified early muscle fibers in the stereotyped outgrowth pattern of axon branches from embryonic neuronal cell bodies by obsserving the effects on axon outgrowth pattern of photoablation of putative embryonic guidance cells, rendered specifically photosensitive by inheritance of a novel fluorescent cell lineage tracer from their precrusor blastomere. 3) To investigate the conditions which are necessary for the biochemical differentiation by which each postmitotic neuroblast gains the capacity to synthesize its cell-specific neurotransmitter, by exposing embryos to anti-mitotic agents at various stages prior to the overt appearance of neurotransmitters. 4) To secure a sset of monoclonal antibodies capable of binding specifically to antigens carried by some but not all of the embryonic neuronal precursor cells, in the hope that some of these antigens are, or are products of, the determinants of cell fate which can be inferred to segregate asymmetrically in successive cleavages, in accord with the stereotyped cell-lineage relations that govern neuronal development in the leech.